The tower of Babel: Survey on concepts and terminology in electrical status epilepticus in sleep and continuous spikes and waves during sleep in North America

Purpose: The terms “electrical status epilepticus during sleep (ESES)” and “continuous spikes and waves during sleep (CSWS)” have been used interchangeably when referring to related but different concepts. In addition, the quantification of epileptiform activity has not been standardized, and different approaches to quantification have been used. The aim of this study was to evaluate the extent to which pediatric neurologists and epileptologists use a homogeneous terminology and conceptualization in CSWS and ESES and to characterize the current understanding of these conditions. Methods: A survey addressing the use of terminology in “ESES” and “CSWS” and the understanding of related concepts was distributed online to all members of the Child Neurology Society and the American Epilepsy Society mailing lists. Surveys were self‐administered and collected using an online survey website ( http://www.surveymonkey.com ). Key Findings: Two hundred nineteen surveys were completed, 137 from the Child Neurology Society mailing list and 82 from the American Epilepsy Society mailing list. ESES and CSWS were considered synonymous by 117 respondents, not synonymous by 61, 21 respondents did not know, and 20 did not respond. Most respondents (63.1%) considered CSWS as a devastating epileptic encephalopathy with severe sequelae even if treated correctly, but 25.1% of respondents indicated that it does not leave sequelae if epilepsy was treated early and another 11.8% noted that cognitive difficulties resolved with age. Cognitive and/or language regression were considered mandatory for the diagnosis of CSWS by only 27% of the respondents. The diagnosis of CSWS was based on electroencephalography (EEG) assessment alone by 31% of respondents. Respondents used different methods for calculation of the epileptiform activity, different EEG samples for calculation, and considered differently the lateralized epileptiform activity. The cut‐off values for percentage of the sleep record occupied by spike‐waves were variable depending on the respondent. There was no agreement on whether these cutoff values were mandatory for the diagnosis of ESES and CSWS. Significance: Our data show that the professionals caring for children with ESES and CSWS in North America use the terms, concepts, and defining features heterogeneously. The lack of a common language may complicate communication among clinicians and jeopardize research in this field. We anticipate that our data will fuel the development of much needed common terminology and conceptualization of ESES and CSWS.     

Neuroprotective effects of progesterone in traumatic brain injury: blunted in vivo neutrophil activation at the blood-brain barrier

Background

Progesterone (PRO) may confer a survival advantage in traumatic brain injury (TBI) by reducing cerebral edema. We hypothesized that PRO reduces edema by blocking polymorphonuclear (PMN) interactions with endothelium (EC) in the blood-brain barrier (BBB).

Methods

CD1 mice received repeated PRO (16 mg/kg intraperitoneally) or vehicle (cyclodextrin) for 36 hours after TBI. Sham animals underwent craniotomy without TBI. The modified Neurological Severity Score graded neurologic recovery. A second craniotomy allowed in vivo observation of pial EC/PMN interactions and vascular macromolecule leakage. Wet/dry ratios assessed cerebral edema.

Results

Compared with the vehicle, PRO reduced subjective cerebral swelling (2.9 ± .1 vs 1.2 ± .1, P < .001), PMN rolling (95 ± 1.8 vs 57 ± 2.0 cells/100 μm/min, P < .001), total EC/PMN adhesion (2.0 ± .4 vs .8 ± .1 PMN/100 μm, P < .01), and vascular permeability (51.8% ± 4.9% vs 27.1% ± 4.6%, P < .01). TBI groups had similar a Neurological Severity Score and cerebral wet/dry ratios (P > .05).

Conclusions

PRO reduces live pericontusional EC/PMN and BBB macromolecular leakage after TBI. Direct PRO effects on the microcirculation warrant further investigation.     

Anatomic guide and sonography for surgical repair of leg muscle lacerations

Background

There were over 110,000 leg laceration cases reported in the United States in 2011. Currently, muscle laceration is repaired by suturing epimysium to epimysium. Tendon-to-tendon repair is stronger, restores the muscle's resting length, and leads to a better functional recovery. Tendons retract into the muscle belly following laceration and surgeons have a difficult time finding them. Many surgeons are unfamiliar with leg muscle anatomy and the fact that the leg muscles have long intramuscular tendons that are not visible in situ. A surgical anatomic guide exists to help surgeons locate forearm tendons; no such guide exists for tendons in the leg.

Materials and methods

The leg tendon ends of 11 cadavers were dissected, measured, and recorded as percentages of leg length. High-frequency ultrasound was used to locate tendon ends in three additional cadavers. These locations were compared with the actual tendon ends located via dissection.

Results

There was little variation in tendon end position within the cadaver group, between men and women or right and left legs. The data are presented as an anatomic guide to inform surgeons of the tendon ends' likely locations in the leg.

Conclusion

The location of leg intramuscular tendon ends is predictable and the anatomic guide will help surgeons locate tendon ends and perform tendon-to-tendon repairs. Ultrasound is a potentially effective tool for detection of accurate location of repairable tendon ends in leg muscle lacerations.     

A review of postoperative feeding regimens in infantile hypertrophic pyloric stenosis

Infantile hypertrophic pyloric stenosis is a condition well known to pediatric surgeons. Postoperative length of hospital stay is a financial concern and remains a potential target for reduction in hospital costs. Ultimately, these costs are directly affected by the ability to effectively advance postoperative enteral nutrition. This review will serve to: 1) identify clinically relevant postoperative feeding patterns following pyloromyotomy, 2) review the relevant literature to determine an optimal feeding pattern, and 3) identify possible preoperative predictors that may determine the success of postoperative feeding regiments.     

Pre- and post-intervention study to assess the impact of a sedation protocol in critically ill surgical patients

Introduction

Sedation and pain management for mechanically ventilated critically ill surgical patients pose many challenges for the intensivist. Even though daily interruption of sedatives and opioids is appropriate in medical intensive care unit (ICU) patients, it may not be feasible in the surgical patients with pain from surgical incision or trauma. Therefore we developed an analgesia/sedation based protocol for the surgical ICU population.

Methods

We performed a two-phase prospective observational control study. We evaluated a prescriber driven analgesia/sedation protocol (ASP) in a 12-bed surgical ICU. The pre-ASP group was sedated as usual (n = 100) and the post-ASP group was managed with the new ASP (n = 100). Each phase of the study lasted for 5 mo. Comparisons between the two groups were performed by χ² or Fisher’s exact test for categorical variables and the Mann-Whitney test for nonparametric variables. A P value <0.05 was statistically significant.

Results

We found a significant reduction in the use of fentanyl (P < 0.001) and midazolam (P = 0.001). We achieved sedation goals of 86.8% in the post-ASP group compared to 74.4% in the pre-ASP (P < 0.001). Mean mechanical ventilations days in pre- and post-ASP group were 5.9 versus 3.8 (P = 0.033).

Conclusion

In our cohort of critically ill surgery patients implementation of an ASP resulted in reduced use of continuously infused benzodiazepines and opioids, a decline in cumulative benzodiazepine and analgesic dosages, and a greater percentage of Richmond Agitation Sedation Scale scores at goal. We also showed reduced mechanical ventilation days.     

Complications following hip arthroscopy: a retrospective review of the McMaster experience (2009–2012)

Background

The use of hip arthroscopy has been steadily rising as technology, experience and surgical education continue to advance. Previous reports of the complication rate associated with hip arthroscopy have varied. The purpose of this study was to report our experience with hip arthroscopy complications at a single Canadian institution (McMaster University).

Methods

We performed a retrospective chart review of 2 hip arthroscopists at the same institution to identify patients who had undergone the index surgery and had been followed for a minimum of 6 months postoperatively. We used a standard data entry form to collect information on patient demographic and clinical characteristics, including age, sex, surgical indication and type of complication if any.

Results

A total of 211 patients underwent 236 hip arthroscopies. The mean age at time of surgery was 37 ± 13 years and mean follow-up was 394 ± 216.5 days. The overall complication rate associated with hip arthroscopy was 4.2% (95% confidence interval 2.3%–7.6%). We identified 4 major and 6 minor complications.

Conclusion

Overall, hip arthroscopy appears to be safe, with minor complications occurring more frequently than major ones. However, surgeons should recognize the possibility of serious complications associated with this procedure. Future research should focus on prospective designs looking for potential prognostic factors associated with hip arthroscopy complications.     

Cyclodextrin Protects Podocytes in Diabetic Kidney Disease

Diabetic kidney disease (DKD) remains the most common cause of end-stage kidney disease despite multifactorial intervention. We demonstrated that increased cholesterol in association with downregulation of ATP-binding cassette transporter ABCA1 occurs in normal human podocytes exposed to the sera of patients with type 1 diabetes and albuminuria (DKD⁺) when compared with diabetic patients with normoalbuminuria (DKD⁻) and similar duration of diabetes and lipid profile. Glomerular downregulation of ABCA1 was confirmed in biopsies from patients with early DKD (n = 70) when compared with normal living donors (n = 32). Induction of cholesterol efflux with cyclodextrin (CD) but not inhibition of cholesterol synthesis with simvastatin prevented podocyte injury observed in vitro after exposure to patient sera. Subcutaneous administration of CD to diabetic BTBR (black and tan, brachiuric) ob/ob mice was safe and reduced albuminuria, mesangial expansion, kidney weight, and cortical cholesterol content. This was followed by an improvement of fasting insulin, blood glucose, body weight, and glucose tolerance in vivo and improved glucose-stimulated insulin release in human islets in vitro. Our data suggest that impaired reverse cholesterol transport characterizes clinical and experimental DKD and negatively influences podocyte function. Treatment with CD is safe and effective in preserving podocyte function in vitro and in vivo and may improve the metabolic control of diabetes.Diabetic kidney disease (DKD) is responsible for nearly half of the incidents of end-stage kidney disease in the U.S. (1), yet our current understanding of the pathophysiological processes responsible for DKD has led to limited improvements in patient outcomes. Multifactorial intervention reduces the rate of progression of DKD but does not prevent end-stage kidney disease in type 1 (T1D) or type 2 diabetes (T2D) (2,3). A key factor for this translation gap is the current lack of adequate mechanistic insight into DKD in humans.The kidney glomerulus is a highly specialized structure that ensures the selective ultrafiltration of plasma so that essential proteins are retained in the blood (4). Podocytes are glomerular epithelial cells that contribute to the glomerular filtration barrier through a tight regulation of actin cytoskeleton remodeling (4). Currently, the diagnosis of DKD relies on the detection of microalbuminuria (5). However, a growing body of evidence suggests that key histological lesions precede the development of albuminuria (6,7); among them, decreased podocyte number (podocytopenia) has been described as an independent predictor of DKD progression (8–12). Although we have previously shown that podocyte insulin resistance and susceptibility to apoptosis is already present at the time of onset of microalbuminuria in experimental models of DKD, the cause of podocyte injury in early DKD remains unknown (13).We used a previously established cell-based assay in which differentiated human podocytes are exposed to 4% patient sera for 24 h (14) to identify new pathways and targets in DKD. Podocytes exposed to the sera of patients with DKD showed increased cholesterol accumulation in association with downregulation of ATP-binding cassette transporter 1 (ABCA1) expression that was independent of circulating cholesterol.ABCA1 is a major regulator of cellular cholesterol homeostasis by mediating efflux to lipid-poor apolipoprotein acceptors in the bloodstream (15). ABCA1 genetic variants are strongly associated with the risk of coronary artery disease (16). Furthermore, the capacity of patient sera to induce ABCA1-mediated cholesterol efflux in macrophages is impaired in patients with T2D and incipient or overt nephropathy (17). Excessive cholesterol accumulation has been described in glomeruli of rodent models of T1D and T2D (18–20) and may contribute to DKD development and progression. Finally, inactivating mutations of ABCA1 result in Tangier disease, which causes premature atherosclerosis and proteinuria (21).Although interventions that increase ABCA1 expression (such as liver X receptor agonists) may be beneficial in DKD, they have a relatively high incidence of adverse events (22) as well as intrinsic lipogenic effects (23). We used β-cyclodextrins, cyclic oligosaccharides consisting of seven β(1-4)-glucopyranose rings, to remove cholesterol from differentiated human podocytes in vitro and from diabetic animals in vivo. The exact mechanism by which cyclodextrins (CDs) remove cholesterol from cells is not completely understood, but the formation of cholesterol/CD inclusion complexes at the membrane surface plays an important role in this process (24).We hypothesized that 2-hydroxypropyl-β-cyclodextrin, which was recently approved by the U.S. Food and Drug Administration (FDA) for the cure of Niemann-Pick disorder (25,26), would be an effective way to sequester cholesterol and to protect podocytes from cholesterol-dependent damage in DKD in vivo and in vitro.